NO dispensing device with emergency dosing system

Description

[0001] The invention relates to a device for delivering gaseous nitric oxide (NO) to a patient comprising an emergency NO dosing system, and intended to be connected to the patient circuit of a mechanical ventilator, i.e. a medical device for administering gas to a patient, which makes it possible to supply the gas at a pre-set flow rate in the event of malfunction, in particular of the control means.

[0002] Nitric oxide (NO) is a gas that, when inhaled, dilates the pulmonary vessels and increases oxygenation by improving gas exchange. It is used to treat various medical conditions, such as pulmonary arterial hypertension of the newborn, or PPHN (for Persistent Pulmonary Hypertension of the Newborn ), Acute Respiratory Distress Syndrome or ARDS observed mainly in adults or pulmonary hypertension in cardiac surgery, as taught in particular by EP-A-560928, EP-A-1516639 or US-A-10,201,564.

[0003] Typically, a small amount of gaseous nitric oxide (NO) (i.e., a few ppm by volume), diluted in nitrogen (N₂), is injected into a gas stream containing oxygen (O₂), which is then inhaled by the patient. The NO concentration, which corresponds to a dosage, is determined by the physician or similar professional. Typically, the gas containing O₂ is an N₂ / O₂ mixture or air, such as medical-grade air. Generally, the NO concentration in the gas inhaled by the patient ranges from 1 to 80 ppm by volume (ppmv), depending on the population being treated, i.e., newborns or adults, and therefore the condition being treated.

[0004] The gas inhaled by the patient can be delivered via a NO delivery device connected to a mechanical ventilator, as described in US-A-5,558,083. The NO delivery device is fluidically connected to one or more gas cylinders containing a mixture of N₂ / NO₂ with an NO concentration typically ranging from 200 to 1000 ppmv. Generally, the NO delivery system includes an NO injection module located in the inspiratory limb of a patient circuit that is fluidly connected, on one side, to the mechanical ventilator and, on the other side, to a breathing interface that delivers the NO-enriched gas to the patient, such as a breathing mask, a tracheal intubation tube, or similar device.

[0005] The NO delivery system also includes a flow sensor that measures the gas flow delivered by the mechanical ventilator (i.e. air or N2 / O2 mixture) in order to determine the amount of NO to be delivered to comply with the dosage set by the doctor.

[0006] The NO delivery system can provide NO dosing by means of a proportional solenoid valve delivering a continuous flow of NO-containing gas, which is associated with a flow sensor, the two components being arranged in the delivery system, as well as an injection line connected to the NO injection module, as described in US-A-5,558,083.

[0007] Another system for issuing NOs is known, for example, from document FR 3 131 538 A1.

[0008] Other systems are available where the proportional solenoid valve is replaced by a plurality of "on or off" type solenoid valves, delivering the gas intermittently, i.e. in the form of pulses, generally at high frequency, whose amplitude and duration ensure the correct amount of gas flowing in the injection line connected to the NO injection module.

[0009] In all cases, known NO delivery systems receive measurements from the flow sensor placed in the inspiratory branch of the patient circuit and adjust in real time the amount of NO to be delivered, according to the desired dosage, by controlling the flow of NO in the injection line.

[0010] Since NO is an effective therapeutic agent, meaning that very low concentrations (i.e., a few ppmv) produce a therapeutic effect, its correct dosage is critically important and medical teams must constantly adjust the dosage according to the patient's condition.

[0011] As the patient's condition changes, the NO concentration must be gradually decreased or increased. For example, in a newborn weaning situation where the condition is improving, it is common practice to gradually decrease the dosage, for example in increments of 1 ppm, until it reaches zero, at which point the NO delivery system can be stopped.

[0012] A gradual decrease in NO concentration helps to avoid the "rebound" effect which can occur in the event of a rapid change in concentration, for example in the event of an abrupt discontinuation of treatment, which can seriously worsen the patient's condition.

[0013] However, nitric oxide (NO) delivery devices are sophisticated electromedical systems susceptible to failures or malfunctions that can significantly impact ongoing therapy. For example, a major electronic malfunction or defect, particularly in the control systems, can lead to device failure and therefore a complete cessation of NO delivery, with the aforementioned negative consequences.

[0014] In such circumstances, the NO delivery device must warn the user, for example by means of an audible alarm signal, that rapid action is required, typically a switch to a backup pneumatic injection mode, i.e. a so-called "emergency" mode, in order to limit as much as possible the adverse effects associated with a discontinuation of therapy.

[0015] Such a switch to backup mode is usually done by actuating a control device, such as a rotary knob, commanding for example a continuous delivery of a fixed flow rate of NO, typically of an N2 / NO mixture, for example on the order of 250 mL / min.

[0016] However, a backup dosing mechanism or system is not without risk, particularly for the following reasons: Its activation requires the presence of a person authorized to perform this action, such as a neonatologist. In a hospital setting, several minutes may pass before this person arrives in the treatment room and the rescue dosage is established, which can lead to a temporary interruption of therapy and expose the patient to a rebound effect. The rescue dosage, such as a pre-set flow rate of an N₂ / NO₂ mixture, does not guarantee that the desired dosage will always be maintained. In particular, when the rescue dosage is significantly lower than the desired dosage, the patient may be exposed to an abrupt change in concentration and potentially subject to significant adverse effects, which is undesirable for obvious reasons of patient safety and treatment efficacy.the emergency dosing is incompatible with certain types of ventilators delivering very small volumes, such as high-frequency oscillating HFO type ventilators (. High Frequency Oscillations This is because it can result in an excessively high concentration of inhaled NO, sometimes even reaching levels dangerous for the patient. Therefore, if the patient is being treated with an HFO ventilator, there is no way to administer NO to the patient, leading to the aforementioned risks associated with the abrupt cessation of treatment.

[0017] It therefore appears that the current emergency dosing mechanisms do not allow for a satisfactory level of safety and that it would be desirable for the patient, in the event of the implementation of emergency dosing due to a malfunction of the NO delivery device, to be able to maintain NO therapy, without interrupting the therapy and / or without worrying about the type of ventilator, i.e. HFO ventilator or other, with which the NO delivery device cooperates.

[0018] In other words, one problem is being able to maintain a dosage, i.e., treatment of the patient with inhaled NO, even in the event of failure or malfunction of the NO delivery device, in particular a total cessation of operation of the means of control of the NO delivery device, in particular due to a breakdown, malfunction or lack of power supply.

[0019] One solution according to the invention relates to a device or apparatus for delivering NO to provide a gas containing NO, typically a NO / nitrogen gas mixture, comprising: a NO injection line for conveying NO-containing gas, a valve device arranged on the injection line to control the flow of NO-containing gas in the injection line, said valve device being configured to be normally in a closed position to prevent any gas flow in the injection line, a flow measurement device arranged on the injection line to perform one or more flow measurements of the NO-containing gas flowing in the injection line, a backup circuit comprising a backup line fluidly connected to the injection line, upstream and downstream of the valve device, said backup line comprising a backup solenoid valve configured to be normally in an open position to allow gas flow in the backup line, and a flow control device, and control means, i.e.a control unit, configured to cooperate with the backup solenoid valve, the flow control device, the valve device and the flow measurement device.

[0020] In the event of a malfunction causing a cessation of cooperation with the control systems, i.e., in the event of a malfunction of the control systems, for example due to a power supply failure: The emergency solenoid valve is configured to move to the open position to allow gas flow in the emergency line of the emergency circuit, the valve device is configured to move to the closed position to stop any gas flow in the injection line, and the flow control device is configured to supply gas at a predetermined emergency gas flow rate, where said emergency gas flow rate: ∘ is determined by the pilot means from at least one gas flow measurement provided by the flow measurement device, during normal operation of the apparatus preceding said malfunction, and ∘ is preset by command of said flow control device by the pilot means, during said normal operation of the apparatus.

[0021] Moreover : A multi-way solenoid valve is arranged on the backup line, downstream of the flow control device, said multi-way solenoid valve comprising: ∘ an inlet channel fluidly connected to the backup line downstream of the flow control device, ∘ a first outlet channel fluidly connected to a first metering line comprising a first calibrated orifice device, and ∘ a second outlet channel fluidly connected to a second metering line comprising a second calibrated orifice device, the first and second metering lines are connected to the backup line, downstream of said first and second calibrated orifice devices, and the first and second calibrated orifice devices have calibrated orifices of different passage cross-sections or diameters,The control means are configured to control the multi-way solenoid valve to direct the gas flow to the first dosing line or, alternatively, to the second dosing line, depending on the gas flow measurement(s) provided by the flow measurement device during normal operation of the device prior to said malfunction.

[0022] Depending on the embodiment considered, the device of the invention may comprise one or more of the following features: The multi-way solenoid valve comprises three ports. The inlet port of the multi-way solenoid valve is supplied with gas via the backup line, typically a NO / N₂ mixture, in the event of a malfunction of the NO delivery device, particularly the pilot unit, typically due to a power supply failure to said pilot unit. A malfunction resulting in a cessation of (all) cooperation with the pilot means includes a fault in said pilot means or a power supply failure to said pilot means. In the event of a malfunction of the NO delivery device, the first outlet port of the multi-way solenoid valve supplies the first metering line comprising the first calibrated orifice device.Alternatively, in the event of a malfunction of the NO delivery device, the second output of the multi-way solenoid valve supplies the second metering line, which includes the second calibrated orifice device. The gas inlet of the multi-way solenoid valve includes an upstream port receiving the gas, typically a NO / N₂ gas mixture. The first output of the multi-way solenoid valve includes a first downstream port supplying the gas, typically a NO / N₂ gas mixture, to the first metering line. The second output of the multi-way solenoid valve includes a second downstream port supplying the gas, typically a NO / N₂ gas mixture, to the second metering line. The control means are configured to, during normal operation of the device, command the backup solenoid valve to be in a closed position, preventing any gas flow in the backup line.The control means are configured to, during normal operation of the device, control the valve device to allow gas circulation in the injection line and preferably to enable at least one gas flow measurement by the flow measurement device. The control means are further configured to, during normal operation of the device, control the flow control device to preset the emergency gas flow rate based on at least one gas flow measurement provided by the flow measurement device. In other words, the flow control device is set prior to any malfunction, i.e., while the NO supply device is operating normally. During normal operation of the device, the flow measurement device is configured to perform several successive flow measurements.During normal operation of the device, the control means are further configured to determine, for example calculate, the emergency gas flow rate (i.e., flow rate of gas containing NO, e.g., NO / N₂ mixture) from one or more flow measurements taken by the flow measurement device. The emergency line connects fluidly to the injection line upstream of the valve device, and upstream or downstream of the flow measurement device, preferably downstream of the flow measurement device. A flow measurement device is arranged on the injection line upstream or downstream of the valve device, preferably downstream of the valve device. The emergency line connects fluidly to the injection line at one end upstream of the valve device and at one end downstream of the valve device so as to bypass said valve device.The backup line connects fluidly to an upstream portion of the injection line located upstream of the valve device, specifically via its upstream end. The backup line connects fluidly to a downstream portion of the injection line located downstream of the valve device, specifically via its downstream end. It includes storage means for storing at least some of the successive flow measurements taken by the flow measurement device; that is, the successive flow measurements are stored by storage means. The storage means are configured to also store one or more lookup tables. The storage means are configured to also store at least one lookup table providing a relationship between pressure and flow rate of the calibrated orifice device(s).The storage means include computer memory, for example, RAM, or the like. The NO injection line carries a gaseous mixture of NO and nitrogen, preferably a NO / N₂ gaseous mixture (i.e., nitric oxide / nitrogen) containing between 100 and 2000 ppmv of NO, typically less than 1000 ppmv of NO, the remainder being nitrogen (and possibly unavoidable impurities). The backup solenoid valve is configured to be normally open, particularly when not controlled by the control means, typically in the event of a malfunction. The backup solenoid valve is of the on / off type. The control means include at least one microprocessor. The control means include an electronic board carrying said at least one microprocessor.The injection line is fluidly connected to a high-pressure line via a pressure regulating device. The high-pressure line and the pressure regulating device are arranged within the NO delivery unit. The NO delivery unit comprises a housing. The NO emergency dosing system is arranged within the housing, specifically the emergency line and the emergency solenoid valve. The emergency line is fluidly connected to the injection line between the pressure regulating device and the valve unit. The valve unit comprises a solenoid valve, preferably a proportional solenoid valve. The flow control device is configured to form or constitute a proportional pressure and flow generation system. The flow control device includes an actuator means cooperating with a pneumatic pressure regulator.The flow control device includes an actuator for controlling the outlet pressure level of the pneumatic pressure regulator. The flow control device includes an actuator with angular displacement adjustment. The actuator includes an electric motor, in particular a stepper motor. The actuator is powered by the power supply, i.e., during normal operation. The actuator includes an electric motor driving a rotary shaft, which is integral with the pneumatic pressure regulator. The pneumatic pressure regulator includes an inlet port and an outlet port in fluidic communication with the backup line.The control means are configured to control the actuator means to operate a displacement, preferably angular, of the pneumatic pressure regulator between at least: ∘ a fully open position corresponding to a maximum opening level, i.e., corresponding to maximum pressure (and maximum flow rate) of the pneumatic pressure regulator. In the fully open position, all the gas flow supplied by the backup line enters the pneumatic pressure regulator, i.e., a maximum flow rate, ∘ a fully closed position corresponding to a fully closed level, i.e., corresponding to zero pressure (and zero flow rate) of the pneumatic pressure regulator.In the fully closed position, no gas flow can pass through the pressure regulator, i.e., a zero flow rate, and advantageously, at least one intermediate position located between the maximum opening and maximum closing positions, thus corresponding to a pressure level at the outlet of the pneumatic pressure regulator between the maximum pressure value and the zero pressure value (i.e., 0 bar). In the intermediate position, only a portion of the gas flow supplied by the backup line enters the pneumatic pressure regulator, i.e., one or more reduced or limited flow rates, lower than the maximum flow rate.The control means are configured to control the actuator to perform an angular displacement of the pneumatic pressure regulator between several angularly distinct positions, offset from one another, including the fully open position, the fully closed position, and several intermediate positions located between the fully open and fully closed positions. Each of these angularly distinct positions corresponds to a given outlet pressure level and gas flow rate, i.e., flow rates between the maximum flow rate, zero flow rate, and intermediate flow rates between these maximum and zero flow rates. The control means are configured to control, command, or monitor the actuator during normal operation of the device, i.e., prior to any malfunction, so as to set or adjust the predetermined backup gas flow rate, i.e., the desired flow rate.The control means are configured to control the actuator to perform a movement, preferably angular, of a moving element of said actuator to a given position corresponding to the preset emergency flow rate. The moving element comprises a rotating shaft, preferably made of metal or a metal alloy. The moving element comprises a rotating shaft capable of being driven by an electric motor. The control means are configured to determine the opening of the pneumatic pressure regulator and / or the preset emergency flow rate from a stored lookup table. The control means are configured to determine an opening of the pneumatic pressure regulator corresponding to the preset emergency flow rate. The lookup table is stored by the storage means, such as in computer memory.It includes power supply means configured to supply electrical current to components requiring electrical power to operate, including control means or other components such as solenoid valves, electric motors, etc. The power supply means include means for connection to mains power (110 / 220V) and / or a battery or similar. The flow control device of the NO emergency dosing system, which forms a proportional system, allows the predetermined emergency gas flow rate to be (pre)set or adjusted prior to any malfunction of the apparatus preventing any cooperation between the control means and the emergency solenoid valve, the flow control device, the valve device, and / or the flow measurement device.The emergency gas flow rate measured by a NO flow sensor located in the NO injection line corresponds to the last flow rate measurement taken by the NO flow measurement device before the malfunction. The first calibrated orifice of the first calibrated orifice device has a first passage diameter (D1), and the second calibrated orifice of the second calibrated orifice device has a second passage diameter (D2) such that 1.5D1 < D2 < 4D1. The first passage diameter (D1) and the second passage diameter (D2) are such that 1.8D1 < D2 < 3D1, preferably D2 is approximately 2D1. The emergency solenoid valve is of the on / off type, capable of only an open state in which it allows gas flow and a closed state in which it stops the gas flow. The flow control device includes an actuator means cooperating with a pneumatic pressure regulator.The actuator means includes a stepper motor, preferably an electric motor. The pneumatic regulator is configured to be adjustable over several pressure levels between 0 and 2 bar relative, preferably less than 1.5 bar relative. The actuator means cooperates with the pneumatic regulator to set a desired output pressure downstream of said pneumatic regulator. The pneumatic regulator includes an internal spring for adjusting the desired pressure level. The actuator means includes a stepper motor configured to adopt several different angular positions, each angular position of the stepper motor corresponding to a given tension of the internal spring of the pneumatic regulator. The desired output pressure level downstream of the pneumatic regulator is determined by the tension of the internal spring of the pneumatic regulator corresponding to the angular position adopted by the stepper motor.In normal operation, the control means are configured to control the multi-way solenoid valve to operate fluid communication between the inlet port of the multi-way solenoid valve and either of the first and second outlet ports of the multi-way solenoid valve so as to pass the gas flow through the first or second calibrated orifice device.

[0023] The invention also relates to a gas supply installation for a patient, i.e., a human being, comprising: at least one NO source containing a NO / N2 gas mixture, an NO delivery device according to the invention, supplied with NO / N2 gas mixture by said at least one NO source, an inspiratory branch of a patient circuit supplied with NO / N2 gas mixture by the NO delivery device, and a medical ventilator, i.e. a respiratory support device, in fluidic communication with the inspiratory branch to supply said inspiratory branch with a respiratory gas containing at least 20% oxygen.

[0024] Depending on the embodiment considered, the gas supply installation of the invention may include one or more of the following features: The medical ventilator delivers air or an oxygen / nitrogen mixture, i.e., as a breathing gas containing at least 21% oxygen by volume. In one embodiment, the medical ventilator includes a motorized blower (i.e., turbine, compressor, or similar) delivering the breathing gas, typically air or an oxygen / nitrogen mixture. In another embodiment, the medical ventilator includes an internal gas circuit comprising one or more proportional valves for routing the gas and controlling its supply, including its flow rate. Such a ventilator is generally supplied with breathing gas from one or more wall outlets supplied by a network of pipes in a hospital or hospital building, typically air or an oxygen / nitrogen mixture. The medical ventilator includes control means, such as one or more electronic control boards.The control system, such as an electronic control board, operates or controls the motorized blower or, as the case may be, the proportional valves of the medical ventilator. The medical ventilator is of the HFO type or includes an HFO function, meaning it is capable of producing high-frequency oscillations. The NO source contains a NO / N₂ gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N₂), conditioned at a pressure between 10 and 250 bar abs, typically above 100 bar abs (before the start of withdrawal). The NO source contains a NO / N₂ gas mixture containing between 100 and 1000 ppmv of NO, the remainder being nitrogen (N₂), conditioned at a pressure between 10 and 250 bar abs, typically above 100 bar abs (before the start of withdrawal). The source of NO is a (or several) pressurized gas cylinder(s).The NO source is one or more gas cylinders with a capacity of between 0.5 and 50 L (water equivalent). The gas cylinder has a cylindrical body made of steel or aluminum alloy. The gas cylinder is equipped with a simple valve (without a regulator) or with an integrated regulator (IR). The gas cylinder is equipped with an IR protected by a protective cover, for example, made of metal or polymer. The patient circuit includes an inspiratory branch and an expiratory branch. The patient circuit includes flexible tubing forming the inspiratory and expiratory branches, typically polymer tubing. The inspiratory and expiratory branches, e.g., flexible tubing, are connected to a junction piece, such as a Y-piece. The inspiratory and / or expiratory branches are fluidically connected to a patient breathing interface, preferably via the junction piece.The patient respiratory interface includes a tracheal intubation tube or breathing mask. The inspiratory and expiratory branches include flexible tubing, for example, made of polymer. The inspiratory and expiratory branches are further fluidically connected to, respectively, the inlet and outlet ports of the medical ventilator. The inspiratory branch of the patient circuit may include a gas humidifier. The gas humidifier is arranged downstream of the NO injection module so that it can humidify the gas before its inhalation administration to the patient.

[0025] According to another aspect, the present disclosure also relates to a method of therapeutic treatment of a person, i.e. a human patient (i.e. adult, child, adolescent or neonate), suffering from pulmonary hypertension and / or hypoxia, causing pulmonary vasoconstrictions or analogs, comprising administration by inhalation to the person in need, of a gas mixture comprising 1 to 80 ppmv of NO and at least 20% vol. of oxygen, preferably at least 21% vol.oxygen, by means of a gas supply installation, such as that described above, comprising a NO delivery device equipped with the NO backup dosing system according to the invention, so as to treat (at least partially) said pulmonary hypertension and / or said hypoxia, which may be caused by one (or more) pulmonary pathology or other pulmonary disorders typically of the type PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or caused by cardiac surgery with the patient being placed under extracorporeal blood circulation (ECC).

[0026] In general, within the scope of the invention: "ppmv" means parts per million by volume, "%vol." means percentage by volume. "NO" refers to nitrogen monoxide. "NO₂" refers to nitrogen dioxide. "N₂" refers to nitrogen. "O₂" refers to oxygen. The terms "concentration," "dose," and "content" are considered equivalent. The terms "piloting," "command," and "control" are considered equivalent and interchangeable. The terms "means of / to / for" are considered entirely equivalent and interchangeable with the terms "device of / to / for" or equivalent terms such as "unit," for example, the terms "piloting means" can be replaced by "piloting device" or "piloting unit," the term "measuring means" can be replaced by "measuring device," etc.By "normal operation": we mean the usual operation of the NO dispensing device for a first period of time (of non-zero duration), in the absence of any failure, malfunction, defect, or other issue. The first period of time typically lasts from one to several minutes, or even hours or days, or longer. By "malfunction": we mean a failure, anomaly, problem, malfunction, defect, or similar event, whether electrical, mechanical, or otherwise, affecting the normal operation of the NO dispensing device, in particular preventing the operation of the device's control means, for a second period of time (of non-zero duration), for example, due to a failure of the control means and / or a power supply failure. The second period of time has a variable duration, for example, from a few seconds to one or more minutes, or tens of minutes, or even longer.

[0027] The invention will now be better understood through the following detailed description, given by way of illustration but not limitation, with reference to the attached figures, among which: Fig. 1 illustrates a schematic embodiment of a gas delivery installation comprising a NO delivery device equipped with an emergency NO dosing system according to the present invention. Fig. 2 à Fig. 5 schematically illustrate the operation of the calibrated orifice / actuator combination of the NO emergency dosing system Fig. 1 .

[0028] Fig. 1 diagrams an embodiment of a gas delivery installation 50 according to the present invention comprising an apparatus or device for delivering NO 1 including an emergency dosing system of NO, associated with a mechanical ventilator 2, i.e. a breathing apparatus delivering a breathing gas.

[0029] This installation 50 is configured to deliver NO in gaseous form to a patient at a desired concentration corresponding to a dosage set by an anesthesiologist or similar physician, typically between 1 and 80 ppmv of NO (i.e. ppm by volume), in particular a NO / N2 mixture flow.

[0030] The medical ventilator 2 delivers a breathing gas containing at least 20 vol.% of oxygen about, preferably at least 21 vol.% of oxygen about, such as air or an O2 / N2 mixture, into a patient circuit 3, in particular into an inspiratory branch 31 of the patient circuit 3, used to deliver and supply the gas to a patient P and to convey the gases exhaled by the patient via an expiratory branch 32 of the patient circuit 3.

[0031] Medical ventilator 2 is a conventional respiratory assistance device which may include, depending on the desired embodiment, either a motorized blower, also called a turbine or compressor, or one or more proportional valves, instead of the motorized blower, which are supplied with gas, for example medical air, by a wall outlet supplied by a hospital network carrying the gas within a hospital establishment.

[0032] In all cases, when the medical ventilator 2 delivers the breathing gas into the patient circuit 3, its operation is controlled by one (or more) electronic control board or similar arranged in the medical ventilator 2. It is electrically powered by means of power supply, such as mains (110 / 220V) and / or an internal battery.

[0033] As an example, a suitable medical ventilator could be the Servo-n Neonatal® from Getinge, which is a proportional valve ventilator with an HFO function. Of course, other medical ventilators with a 2-way valve could also be suitable.

[0034] As seen on Fig. 1 The inspiratory branch 31 and the expiratory branch 32 are fluidically connected to a junction piece 33, such as a Y-piece or similar, in fluidic communication with a respiratory interface 30 allowing the gas to be delivered to patient P or, conversely, to be collected from patient P. The respiratory interface 30 can, for example, be a face mask, a tracheal intubation tube or other.

[0035] The inspiratory branch 31 and expiratory branch 32 include conduits, pipes, tubes, passages, tubing or the like, for example flexible polymer tubing, suitable for and configured to convey gas flows.

[0036] The respiratory gas flows in the inspiratory branch 31 from the mechanical ventilator 2 towards patient P, while the exhaled gases enriched in CO2 flow in the expiratory branch 32 towards the mechanical ventilator 2 where they are discharged into the atmosphere.

[0037] A flow sensor 100 and a NO injection module 110 are arranged in the inspiratory limb 31. The flow sensor 100 is generally arranged between the NO injection module 110 and the mechanical ventilator 2 so as to be able to measure the gas flow from the mechanical ventilator 2. The inspiratory limb 31 may also include a humidifier (not shown) to humidify the gas delivered to the patient, which is preferably arranged downstream of the NO injection module 110, i.e. between the NO injection module 110 and the respiratory interface 30, such as a tracheal intubation tube.

[0038] The flow sensor 100 is used to measure the gas flow, e.g. air or O2 / N2 mixture, supplied by the mechanical ventilator 2 and circulating in the inspiratory limb 31. The measurements taken are provided, directly or indirectly, to the control means 130 of the NO delivery device 1 which use them to control or adjust the quantity of NO supplied by the NO delivery device 1, i.e. the NO flow, typically of NO / N2 gas mixture, supplied by the NO delivery device to the NO injection module 110, as explained below.

[0039] For example, a mass flow sensor, a differential pressure sensor, or any other suitable sensor can be used.

[0040] In the implementation of Fig. 1 The flow sensor 100, for example, is of the differential pressure measurement type, meaning that the flow sensor 100 includes an internal restriction 101 which creates a pressure drop generating a differential or pressure gradient when a gas flow passes through this internal restriction 101. The flow sensor 100 includes upstream chambers 120 and downstream chambers 121 which are separated by a wall 122 through which a gas passage passes so as to form the internal restriction 101.

[0041] Upstream pressure measurement lines 103 and downstream 102 are fluidically connected to the flow sensor 100 at connection sites located upstream and downstream of the internal restriction 101, in particular at the upstream chambers 120 and downstream chambers 121, in order to carry out pressure measurements of the circulating gas flow, before and after pressure loss, i.e. of air or an O2 / N2 mixture.

[0042] The pressure difference created by the internal restriction 101 is determined by a differential pressure sensor 104 connected to the flow sensor 100 via the upstream pressure lines 102 and downstream pressure lines 103 which form pressure measurement conduits and provide the differential pressure sensor 104 with pressure measurements of the circulating flow, before and after pressure loss.

[0043] Preferably, the differential pressure sensor 104 is integrated into the housing 10 of the NO delivery device 1, as illustrated in Fig. 1 .

[0044] The sensor 104 is also electrically connected to a control unit 130, also called a controller or control means, and / or transmits pressure measurements to it so that they can be processed by computer, in particular to regulate or adjust the start of NO, typically of NO / N2 mixture, supplied by the NO delivery device 1 to the NO injection module 110.

[0045] The NO 110 injection module injects the flow of NO, i.e. NO / N2, into the gas flow circulating in the inspiratory branch 31 to make the desired mixture, i.e. typically a NO / O2 / N2 mixture containing NO at the desired concentration corresponding to the dosage set by a doctor or similar, which is typically between 1 and 80 ppmv, generally between 5 and 40 ppmv of NO, the remainder being oxygen (>20 vol.% approximately) and nitrogen, or even unavoidable impurities (e.g. argon...) and water vapor, particularly when a humidifier is present downstream of the NO 110 injection module.

[0046] Advantageously, a bypass line 105 can be provided to connect to the downstream pressure line 103 in order to convey the pressure information in said downstream pressure line 103 to a pressure sensor 106, typically of the relative type. This pressure sensor 106 measures the pressure in the upstream chamber 120 of the flow sensor 100 and can return this value, via an electrical connection, to the control unit 130 for compensation purposes, considering that the actual flow value through the flow sensor 100 depends mainly on the differential pressure measurement 104 but is also affected by the relative pressure 106 upstream of the flow sensor 100.

[0047] The control unit 130 includes a data processing system, specifically for measurements from sensors 100, 104, and 106, typically comprising one or more microprocessors mounted on one or more electronic boards and implementing one or more algorithms, i.e., one or more computer programs. Of course, the control unit 130 can also be configured to control other electromechanical components integrated into the housing 10 of the NO delivery device 1.

[0048] More specifically, the control unit 130 is configured to process and / or utilize the measurements, i.e. the pressure measurement signals or pressure values, transmitted by the differential pressure sensor 104 cooperating with the flow sensor 100, and / or by the pressure sensor 106. Advantageously, the control unit 130 has a pre-recorded, i.e. stored, lookup table which allows a determination of the gas flow circulating in the inspiratory branch 31, i.e. passing through the flow sensor 100, i.e. transforming a pressure value transmitted by the pressure sensor 104, such here as a differential pressure sensor, into a flow value passing through the flow sensor 100, possibly compensated by the value returned by the pressure sensor 106.

[0049] In general, determining the flow rate of the gas flow (e.g. air) through the flow sensor 100 then allows the amount of NO (i.e. the NO / N2 flow rate) to be calculated to be injected into the gas flow circulating in the inspiratory limb 31 by the NO injection module 110 in order to deliver NO to the patient at the desired concentration corresponding to the dosage set by an anesthesiologist or similar physician, typically between 1 and 80 ppmv of NO (i.e. ppm by volume).

[0050] In other words, using the pressure measurement returned by the differential pressure sensor 104 and the stored lookup table, the control unit 130 can determine the gas flow rate (e.g. air or N2 / O2 with O2 content > 21% vol.) from the mechanical fan 2 and the amount of NO to be added, via the NO injection module 110, in order to obtain the desired NO concentration.

[0051] As already mentioned, the final gas mixture obtained at the NO 110 injection module then mainly comprises nitrogen (N 2 ), oxygen (O 2 ) at a content of at least 20 to 21% vol., and NO at a content typically between 1 and 80 ppmv, possibly with unavoidable impurities and / or water vapor, especially when a gas humidifier is present.

[0052] More specifically, based on the gas flow rate (i.e. air or N2 / O2) circulating in the inspiratory limb 31, which has been determined using the flow sensor 100, the control unit 130 determines the amount of NO, typically of NO / N2 mixture, to be added to the gas having an O2 content > 20% vol. (e.g. air or N2 / O2) circulating in the inspiratory limb 31 in order to obtain the desired final NO concentration.

[0053] The NO₂ delivery device is supplied with gaseous NO, typically a gaseous NO / N₂ mixture, from an NO₂ source fluidly connected to the NO₂ delivery device, in particular to a high-pressure line 116 of said NO₂ delivery device, by a supply line 251, such as a flexible conduit or the like. Typically, the NO₂ source is one or more pressurized gas cylinders containing a NO / N₂ mixture with an NO concentration generally between 100 and 30,000 ppmv.

[0054] The NO / N 2 mixture is supplied to the injection module 110 by the NO delivery device 1, via an injection line 111, such as a flexible gas line, which is fluidly connected to the high pressure line 116 of the NO delivery device 1, which includes a high pressure inlet 116a fluidly connected to the NO source to be supplied with NO / N 2 under pressure, e.g. 10 bar abs.

[0055] The high-pressure line 116, for example a gas passage or conduit, includes a pressure regulator 115 that reduces the pressure of the NO / N₂ mixture to a stable value, for example approximately 2 bar abs or any other suitable pressure. The outlet port of the pressure regulator 115 thus provides a stable pressure in the upstream portion of the injection line 111.

[0056] A valve device 113, such as a solenoid valve, advantageously a proportional solenoid valve, for example the miniature VSO series solenoid valve available from Parker, is arranged in the NO delivery device 1 to control the flow of gaseous NO within the injection line 111.

[0057] The gas flow rate in the injection line 111 is measured by a flow measurement device or NO flow sensor 112, arranged on the injection line 111, preferably located downstream of the valve device 113, as shown on Fig. 1 .

[0058] The pressure regulator 115, the valve or solenoid valve device 113, the NO flow sensor 112 and an upstream portion of the injection line 111 are therefore arranged in the housing 10 of the NO delivery device 1.

[0059] The valve device 113 is configured to normally be in a closed position (i.e. a closed state) to prevent any gas circulation in the injection line 111. To switch to the open position, the valve device 113 must be controlled by the pilot means 130, as is the case during normal operation of the NO delivery device 1.

[0060] Furthermore, a backup NO dosing system is planned, i.e. a backup circuit 200, arranged in the box 10 of the NO delivery device 1, which is configured to operate in the event of a malfunction of the NO delivery device 1, as explained below.

[0061] The emergency circuit 200 includes (at least) one emergency line 201, also called a bypass line, such as a gas passage or conduit, or similar.

[0062] In the proposed embodiment Fig. 1 , the emergency line 201 of the emergency circuit 200 connects fluidly to the injection line 111 at a first connection site 111a, i.e. upstream, located between the pressure regulator 115 and the valve device 113, and at a second connection site 111b, i.e. downstream, located downstream of the valve device 113 and, preferably, downstream of the NO flow sensor 112.

[0063] In other words, the valve device 113 and preferably the NO flow sensor 112 are located between the first and second connection sites 111a, 111b of the backup line 201, i.e. the backup line 201 bypasses, the valve device 113 and preferably the NO flow sensor 112 arranged on the injection line 111.

[0064] Alternatively, according to another embodiment, the second connection site 111b can be located between the valve device 113 and the NO flow sensor 112.

[0065] In all cases, the gas flows in the backup line 201 in the direction from the first connection site 111a to the second connection site 111b.

[0066] The emergency circuit 200 also includes an emergency solenoid valve 202 and a flow control device 210 which are arranged on the emergency line 201 and which serve to control the gas flow within the emergency circuit 200, typically within the emergency line 201.

[0067] A 3-way solenoid valve 205, i.e. of type 3:2, is arranged on the backup line 201, downstream of the flow control device 210. It is controlled by the pilot means 130.

[0068] The 3-way solenoid valve 205 comprises an upstream port 201a, a first downstream port 205a, and a second downstream port 205b, in fluidic communication. The selection of fluidic communication between the upstream port 201a and the first downstream port 205a or, alternatively, the second downstream port 205b is operated by the pilot means 130, as described below.

[0069] The 3-way solenoid valve 205 is of the bistable type, that is to say that in the absence of electrical control by the pilot means 130, for example in the event of malfunction, typically in the event of loss of electrical supply, the fluidic communication existing between the upstream port 201a and the first downstream port 205a or the second downstream port 205b is maintained, that is to say it remains in the state in which it was before malfunction.

[0070] As an example, one can use the solenoid valve 205 referenced HDI available from The Lee Company ®< .

[0071] The first downstream port 205a of the solenoid valve 205 is in fluidic communication with a first dosing line 206, in which is arranged a first calibrated orifice device 208, while the second downstream port 205b of the solenoid valve 205 is in fluidic communication with a second dosing line 207 in which is arranged a second calibrated orifice device 209.

[0072] The first and second calibrated orifice devices 208, 209 have different characteristics in terms of the cross-section of their respective calibrated orifices, e.g., different diameters. Thus, the first calibrated orifice of the first calibrated orifice device 208 may have a first cross-sectional diameter D1 and the second calibrated orifice device 209 has a second cross-sectional diameter D2, such that D1 < D2, preferably 1.5D1 < D2 < 4D1.

[0073] For example, the first calibrated orifice of the first calibrated orifice device 208 may have a first passage diameter D1 of the order of 25 µm and the second calibrated orifice of the second calibrated orifice device 209 has a second passage diameter D2 of the order of 50 µm, that is to say that D2 is preferably equal to about 2.D1.

[0074] For example, calibrated orifices available from O'Keefe Control® under references BLP-1-SS and BLP-2-SS can be used. Of course, other calibrated orifices of different diameters and / or shapes can be used.

[0075] Downstream of the first and second calibrated orifice devices 208, 209, the first and second metering lines 206, 207 meet at a connection point 201b, called a node, and also connect, at this same point 201b, to the downstream section of the backup line 201. This backup line 201 then connects fluidly (downstream of point 201b) to the injection line 111 at the second connection point 111b. In other words, the first metering line 206 and the second metering line 207 connect at node 201b to form the downstream section of the backup line 201.

[0076] The emergency solenoid valve 202 is configured to normally be in an open position (i.e., open state) to allow gas circulation in the emergency line 201; that is, it allows the gas flow to pass through when it is not or is no longer controlled by the pilot unit 130. During normal operation of the NO 1 delivery device, the emergency solenoid valve 202 is therefore controlled by the pilot means 130 to be in a closed position (i.e., closed state) to prevent the NO / N2 flow from using the emergency line 201.

[0077] The 202 emergency solenoid valve is preferably an on / off type solenoid valve with two possible states: an open state allowing gas flow and a closed state preventing gas flow. It is controlled by the 130 control unit. For example, a solenoid valve from the IMI Norgren® Picosol series or the Lee Company® HDI series can be used.

[0078] As already mentioned, the emergency solenoid valve 202 is normally open, that is to say that in the absence of an electrical command from the control unit 130, the emergency solenoid valve 202 is in the open state, i.e. open position, which then allows the gas from the NO source to take the emergency line 201 from the first connection site 111a towards the second connection site 111b.

[0079] On the other hand, the control unit 130 commands the closing of the emergency solenoid valve 202, that is to say its change from the open state to the closed state, i.e. in the closed position, any circulation of gas in the emergency line 201 is prevented, in particular when a flow is not desired, typically in normal operation.

[0080] In other words, the control means 130, i.e. the control unit, are configured to cooperate with the emergency solenoid valve 202, the flow control device 210, the valve device 113 and the flow measurement device 112, during normal operation of the NO delivery device 1, in order to direct the gas flow to the injection line 111 and prevent it from flowing into the emergency line 201, and vice versa in case of malfunction, as explained below.

[0081] In the implementation of Fig. 1 , the flow control device 210 comprising an actuator means 203, preferably adjustable by angular displacement, typically a stepper motor, cooperating with a pneumatic pressure regulator 204 and thus forming a variable pressure system enabling control of the flow rate and pressure of the gas flow.

[0082] When the emergency solenoid valve 202 is open, i.e., not controlled by the control unit 130, typically in the event of a power failure or malfunction of the control unit 130, the pressure in the upstream portion 201c of the emergency line 201 (i.e., between the first connection point 111a and the pneumatic regulator 204) is equal to the relief pressure of the pressure regulator 115, for example, here equal to 2 bar rel. (14 psig). This same pressure is also present at the inlet of the pneumatic regulator 204, which is connected to the emergency line 201.

[0083] The pneumatic regulator 204 can be set to several different pressure levels, typically up to 2 bar relative, for example between approximately 0 and 1.4 bar relative (i.e., 0-20 psi), depending on the tension of its internal spring. A pneumatic regulator available from Beswick Engineering® under part number PRDB can be used, for example.

[0084] The actuator means 203, namely here a stepper motor, is mechanically coupled to the pneumatic regulator 204 so that a given angular position of the stepper motor influences the tension of the internal spring of the pneumatic regulator 204 and thus fixes an output pressure downstream of said pneumatic regulator 204.

[0085] In other words, the stepper motor can, depending on its angular position, determined by the control means 130, control the pneumatic regulator 204, in particular by acting on the tension of its internal spring, to go from a closed position, i.e. delivering zero pressure at its output, to an open position, delivering maximum pressure at its output, typically less than 2 bar relative, for example on the order of 1.4 bar relative (i.e. about 20 psig).

[0086] Of course, depending on the angular position of the stepper motor, i.e. according to its "number of steps", the pneumatic regulator 204 can adopt one (or more) intermediate position, thus delivering a pressure between a minimum, for example 0 bar relative, and a maximum typically less than 2 bar relative, for example 1.4 bar relative.

[0087] Therefore, the resolution in terms of adjustable pressures downstream of the pneumatic regulator 204 depends on the fineness and number of steps defining a given position of the stepper motor, i.e. of the actuator means 203, of its next position.

[0088] So, Fig. 2 This represents the evolution of the output pressure of the pneumatic regulator 204 as a function of the number of steps (i.e., the position of the stepper motor), determined by the control means 130. It shows that the pressure increases linearly with the number of steps. More precisely, it can be seen that the maximum output pressure of the pneumatic regulator 204 is limited to 12 psig (830 mb rel.) but that it could be higher, typically up to 20 psig (1.4 bar rel.), by increasing the number of steps.

[0089] More generally, the pressure at the outlet of the pneumatic regulator 204 is then found at the upstream port 201a of the solenoid valve 205 which is arranged on the backup line 201 downstream of the pneumatic regulator 204.

[0090] In normal operation, the multi-way solenoid valve 205, here with three ways, is also controlled by the pilot means 130 to achieve fluid communication between its inlet channel which is fluidly connected to the backup line 201 downstream of the flow control device 210, and one or the other of its first outlet channel which is fluidly connected to the first dosing line 206, and of its second outlet channel which is fluidly connected to the second dosing line 207, that is to say between its upstream port 201a and one of its downstream ports 205a, 205b.

[0091] The outlet pressure of the pneumatic regulator 204 then propagates into the upstream portion 206a of the first metering line 206 located upstream of the first calibrated orifice 208 or, as the case may be, into the upstream portion 207a of the second metering line 207 located upstream of the second calibrated orifice 209.

[0092] In other words, during the normal operation of the device 1, the control means 130 control the 3-way solenoid valve 205 to operate a fluidic communication between the inlet of said solenoid valve 205 and one or the other of the first and second outlets of the 3-way solenoid valve 205 so as to circulate the gas flow in one or the other of the dosing lines 206, 207, therefore through the first or the second calibrated orifice device 208, 209 which include different passage sections or diameters of their calibrated orifices D1, D2.

[0093] Generally speaking, for any calibrated orifice, there is a relationship between the pressure upstream of the calibrated orifice and the flow rate through it, since the flow rate depends on the dimensions of the orifice. Indeed, the flow rate through a calibrated orifice is related to the pressure differential between the upstream and downstream pressures of that calibrated orifice.

[0094] So, Fig. 3 represents the relationship linking the pressure (in psig) upstream of the first orifice of the first calibrated orifice device 208 and the flow rate (in mL / min) through it, i.e. circulating in the downstream portion 206b of the first dosing line 206.

[0095] We can see that the flow rate increases as the upstream pressure increases. This increase does not follow a linear law but rather a "square root" type, as widely documented in the literature.

[0096] Therefore, here, depending on the position of the solenoid valve 205, the flow through the first calibrated orifice of the first calibrated orifice device 208 depends on the difference in pressures prevailing respectively in the upstream 206a and downstream 206b portions of the first dosing line 206, and conversely, the flow through the second calibrated orifice of the second calibrated orifice device 209 depends on the difference in pressures prevailing respectively in the upstream 207a and downstream 207b portions of the second dosing line 207.

[0097] Preferably, the pressure downstream of the first and second calibrated orifices, i.e., downstream of the two calibrated orifice devices 208, 209 (i.e., in the downstream portions 206b, 207b), is otherwise considered negligible. However, additional measuring means, such as an additional pressure measuring device, may be arranged to perform a pressure measurement downstream of the first and second calibrated orifices, for example, in the region of node 201b of the backup line 201, and used for pressure compensation purposes to increase the accuracy of the flow control device 210, as detailed below.

[0098] Furthermore, the flow rate expression also corresponds to a position of the stepper motor 203, expressed in steps, as shown in Fig. 4 , based on the linear relationship linking the position of the motor 203 to the output pressure of the pneumatic regulator 204, as illustrated in Fig. 2 .

[0099] So, Fig. 4 This shows that a step count of 0 corresponds to a closed position of the pneumatic regulator 204, and each step corresponds to a change in position of the stepper motor 203, slightly opening the pneumatic regulator 204 to allow the gas flow. For example, 50 steps result in a flow rate of approximately 4 ml / min, while 100 steps result in a flow rate of approximately 5.5 ml / min.

[0100] From there, by entering a lookup table linking a number of steps (i.e. a position of the stepper motor 203) and a resulting flow rate, the control means 130 can "(pre-)set" the backup dosing system or circuit 200, during the normal operation of the device 1, as explained below, so that it is operational in the event of a malfunction of the control unit 130, typically in the event of a power failure of the control unit 130.

[0101] In other words, during normal operation of device 1, the control means 130 control the pneumatic regulator 204 to adjust or fix the position of the stepper motor 203 on a determined number of steps corresponding to a desired gas flow rate.

[0102] Similarly, during normal operation of device 1, when the control means 130 command the 3-way solenoid valve 205 to establish fluid communication between its upstream port 201a and, for example, its second downstream port 205b, it is possible to establish, as before, a lookup table linking a number of steps (i.e., a position of the stepper motor 203) and a resulting gas flow rate, circulating then in the downstream portion 207b of the second metering line 207, as illustrated in Fig. 5 .

[0103] Since the diameter of the second calibrated orifice 209 is larger than that of the first calibrated orifice 208, the resulting flow rate at a similar "step" (i.e., similar position) is greater. For example, for 50 steps, a flow rate of approximately 15 ml / min is obtained (4 ml / min for the first calibrated orifice 208).

[0104] In other words, depending on the configuration of the 3-way solenoid valve 205, the control unit 130 can have a lookup table linking a given control level (i.e. step) to a gas flow through the first or, alternatively, the second calibrated orifice 208, 209 towards the injection line 111 and entering it at the second connection site 111b.

[0105] All of these (pre-)settings are carried out during the proper operation of the device 1, that is to say during its normal operation before any malfunction of the control unit 130, in particular when it is no longer supplied with electrical current, therefore no longer functioning.

[0106] This is then used to ensure the delivery of a backup NO flow (i.e. NO / N2 flow), even in the event of a malfunction of the control unit 130, i.e. when it is no longer supplied with electrical current, therefore no longer works, since all the settings have already been made, before the malfunction.

[0107] Thus, in normal operation of the NO 1 delivery device, i.e., when the control unit 130 is operational and normally supplied with electrical current, the emergency solenoid valve 202 is controlled by the control unit 130 to be closed, which prevents any gas circulation in the emergency circuit 200. Fig. 1 Whereas, in the event of a malfunction of device 1 rendering the control unit 130 inoperative, such as an electrical fault, the emergency solenoid valve 202 can no longer be controlled by the control unit 130 and therefore opens to allow gas to flow into the emergency circuit 200, while the solenoid valve 113 closes, as already explained. The gas flow circulating in the emergency circuit 200 is then subject to the (pre-)settings made before the malfunction, i.e., the position of the stepper motor, the direction of the flow towards the first or second calibrated orifice device 208, 209...

[0108] In general, using a stepper motor as an actuator means 203 is particularly recommended because, unlike solenoid valves 202, 113 which take a rest position in the event of a power outage, namely an open position for the on / off solenoid valve 202 and a closed position for the proportional solenoid valve 113, the position of the stepper motor does not change, i.e. remains permanent, and fixed according to the last command imposed, and this independently of any power supply.

[0109] In other words, the tension of the internal spring of the pneumatic regulator 204 has a fixed value and is equal to the last control value from the control means 130 and received by the stepper motor, i.e. a given position corresponding to a given number of steps, during the normal operation of the device 1.

[0110] In the event of gas supply to the pneumatic regulator 204, i.e. when the emergency solenoid valve 202 opens due to a lack of control by the pilot means 130, the tension of the internal spring of the pneumatic regulator 204 generates a fixed pressure downstream of the pneumatic regulator 204, which is then found at the upstream port 201a of the solenoid valve 205.

[0111] Of course, the present invention is not limited to a stepper motor type actuator. Indeed, any other actuator that maintains its position in the event of a power failure and that can be coupled to a mechanical mechanism to define or constitute a variable pressure system can be used, such as a linear motor or other.

[0112] In general, during its normal operation, the NO 1 delivery device is also electrically powered by an electrical supply, such as the mains (110 / 220V) or an internal battery, in order to allow the proper operation of its components requiring electrical current to function, in particular the actuator 203, such as an electric stepper motor, the control unit 130, the solenoid valves 202, 113, 205 or others.

[0113] In addition, the NO 1 delivery device also includes storage means, such as computer memory, to store data, information or other, for example one or more lookup tables, as explained above, gas flow measurements carried out by the flow measurement device 112, or others.

[0114] In general, in the event of a major failure in the operation of the NO delivery device 1, such as a power supply failure, for example caused by a break in its power supply cable caused by vibrations during patient transport for example, it must be possible to continue to provide treatment of the patient with inhaled NO despite the malfunction causing a stoppage of operation of the control means 130, typically due to a power supply failure.

[0115] To this end, the device 1 of the invention is configured so that, in the event of such a failure, the emergency solenoid valve 202 goes into the open position to allow gas to circulate in the emergency line 201, while, at the same time, the valve device 113 goes into the closed position to stop any gas circulation in the injection line 111, which makes it possible to supply, via the emergency line 201 and the flow control device 210, the gas at a pre-set emergency gas flow rate.

[0116] In fact, during the normal operation of device 1 prior to the malfunction, said emergency gas flow rate is determined by the control means 130 from one or more gas flow measurements provided by the flow measuring device 112 to the control means 130. The control means 130 can then pre-set the flow control device 210 and the solenoid valve 205 so that they can deliver the gas at the pre-set emergency gas flow rate.

[0117] In other words, the control means 130 determine the emergency gas flow to be administered in the event of a failure or other malfunction, based on the gas flow measurements provided by the flow measurement device 112 during the normal operation of the device 1, and act on the flow control device 210 and the 3-way solenoid valve 205 to adjust this predetermined emergency gas flow, for example by adjusting the pneumatic regulator 204, as explained above.

[0118] More generally, the operation of the gas delivery installation 50 comprising the NO 1 delivery device of the invention is overall as follows.

[0119] As illustrated in Fig. 1 The NO delivery device 1 cooperates with a mechanical ventilator 2 to provide therapeutic support to patient P. As already explained, the gas flow rate (i.e., air or N2 / O2) from the mechanical ventilator 2 and circulating in the inspiratory limb 31 of the patient circuit 3 is continuously measured by the flow sensor 100 and the control unit 130. The flow rate measurement(s) performed by the flow sensor 100 allows the control unit 130 to determine, in real time, the NO flow rate that must circulate in the injection line 111 to the NO injection module 110 in order to inject the quantity of NO into the airflow from the ventilator 2 so as to obtain the desired final NO concentration, typically between 5 and 80 ppmv, in the final NO / O2 / N2 gas mixture administered to patient P.

[0120] In normal operation, i.e. without failure or malfunction, in order not to introduce additional flow from the backup line 201 into the injection line 111, the control unit 130 controls the solenoid valve 202, which is preferably of the on / off type, in the closed position and, in parallel, will control the actuator 203, like a stepper motor, in order to pre-set the pneumatic regulator 204 by defining a tension level of its internal spring, preferably according to the position adopted by the stepper motor 203, as explained above.

[0121] This is operated by the pilot unit 130 from one or more flow measurements from the flow measurement device 112.

[0122] More specifically, the pilot unit 130 first performs an average of the NO flow rate (i.e. of the NO / N2 mixture) that has flowed through the injection line 111 for a given time, for example for 1 minute or over a longer period of time (but the flow rate must then be converted into L / min or ml / min), during the normal operation of the device 1.

[0123] The control unit 130 therefore estimates a fixed average NO flow rate value (in L / min or ml / min) allowing it to get close to the desired NO concentration.

[0124] Thus, in Tab.1, the fixed average NO flow rate (in ml / min) is given for different selected NO concentrations (in ppmv), i.e. dosages, resulting from different minute ventilations (L / min) measured by the flow sensor 100, which is used by the control means 130 to determine the NO flow rate to be delivered in real time. Tab. 1 Ventilation Minute (L / min) Teneur en NO (posologie) (en ppmv) 2 4 6 15 5 0,1 0,2 0,3 0,8 10 0,5 1 1,5 3,8 20 1 2 3 7,5 40 2 4 6 15 60 4 8 12 30,1 80 6 12 18,1 45,1

[0125] It is observed that for an average minute ventilation of 2 L / min measured by the flow sensor 100, and for a NO dosage of 5 ppmv, the average NO flow rate is 0.1 ml / min, and increases as the minute ventilation increases and / or the NO dosage increases. The average NO flow rate can therefore vary from 0.1 to 45 ml / min.

[0126] In order to take into account this large flow rate range, as already mentioned, the emergency dosing system 200 is equipped with a first and a second calibrated orifice device 208, 209, arranged on the first and second dosing lines 206, 207 arranged downstream of the pneumatic regulator 204.

[0127] As illustrated in Fig. 4 The first calibrated orifice device 208 is configured to generate relatively low flow rates over a wide pressure range, for example, flow rates below 10 ml / min, while the second calibrated orifice device 209 is configured to generate higher flow rates that can exceed 50 ml / min, as illustrated in Fig. 5 .

[0128] However, in the 0-10 ml / min range, we note that the relationship between the flow rate and the position of the stepper motor is unfavorable to the calibrated second orifice device 209 because a small variation in the position of the stepper motor 203 causes a significant variation in flow rate, which can impair the accuracy of the generated flow rates.

[0129] Therefore, the system is configured so that the gas flow passes through the first calibrated orifice device 208 when the average NO flow rate is low, i.e. less than or equal to 10 ml / min, and through the second calibrated orifice device 209, for higher average NO flow rates, i.e. greater than 10 ml / min.

[0130] The control unit 130 then operates a specific control of the 3-way solenoid valve 205 according to the average NO flow rate to operate a fluidic communication between its upstream port 201a and its first downstream port 205a (if flow rate < 10 ml / min) or, where applicable, its second downstream port 205b (if flow rate > 10 ml / min), in order to direct the emergency NO flow rate towards the first dosing line 206 through the first calibrated orifice device 208 or, where applicable, towards the second dosing line 207 through the second calibrated orifice device 209.

[0131] In normal operation, the control unit 130 averages the NO flow rate and then uses the value thus determined to control the 3-way solenoid valve 205 to select the first or second dosing line 206, 207, therefore the first or second calibrated orifice device 208, 209, intended to take charge of the NO flow, i.e. which will be used to operate the emergency dosing of NO, in case of malfunction of the NO device 1, in particular in case of failure of power supply to the flow sensor 100 or the control unit 130.

[0132] Furthermore, the control unit 130 performs a conversion using a stored lookup table or similar method, taking into account the selected calibrated orifice, i.e., the first or second calibrated orifice device 208, 209, in order to control the actuator 203 of the flow control device 210, such as a stepper motor, and to define a tension level for the internal spring of the pneumatic regulator 204 in order to allow a flow of NO circulating in the backup line 201 of the backup system 200 that is equal to the calculated value of fixed average NO. This calculated value of average NO thus serves as the backup gaseous NO flow in the event of a malfunction of the device 1.

[0133] In normal operation, no gas flows through the backup line 201 because the on / off solenoid valve 202 is closed. The gas flows normally through the injection line 111, via the proportional solenoid valve 113 and the flow meter 112, before being supplied to the NO injection module 110, which mixes the NO flow with the air or similar flow from the fan 2.

[0134] Therefore, in the event of a major failure of the NO 1 delivery device and / or an interruption of its power supply, with the exception of actuator 203, solenoid valve 205, and pressure regulator 115 (which operates purely pneumatically), all electromechanical actuators, particularly the solenoid valves, return to their rest position because the control unit 130 is also without power. Furthermore, the various sensors are left without power and thus unable to communicate and / or control other components.

[0135] Thus, the proportional solenoid valve 113 returns to its rest position, namely its closed position preventing any passage of gas, while the solenoid valve 202 simultaneously returns to its rest position, namely its open position, thus allowing the passage of gas from the NO source into the emergency line 201 of the emergency circuit 200, and its circulation until it reaches the second junction site 111b, then the downstream part of the injection line 111.

[0136] The NO / N mixture then flows in the emergency line 201 at the pre-set emergency flow rate which is controlled by the association of the pneumatic regulator 204, in particular by its generated pressure, and the selected calibrated orifice, i.e. the first calibrated orifice device 208 or the second calibrated orifice device 209, knowing that, as already explained, the last valid value of the fixed average NO flow rate was then determined by the control unit 130 during the normal operation of the device 1, prior to its malfunction.

[0137] The NO / N 2 relief flow which joins the injection line 111 (in 111b) can then be injected into the inspiratory branch 31 of the patient circuit 3 via the NO 110 injection module, as already mentioned.

[0138] In general, according to the invention, the flow control device 210 is configured to supply the gas, i.e. NO / N 2, at a predetermined emergency gas flow rate, where said emergency gas flow rate is determined by the pilot means 130 from one (or more) gas flow measurement provided by the flow measurement device 112, during normal operation of the device 1 prior to the malfunction, for example the last flow value having been measured before the malfunction affecting the proper operation of the device 1.

[0139] The flow value is preset within the flow control device 210, for example by acting on the tension of the internal spring of the pneumatic regulator 204 of the flow control device 210 as explained above, by control, i.e. presetting, of the flow control device 210 by the control means 130. The presetting takes place, i.e. is operated or carried out, during the normal operation of the device 1.

[0140] Of course, when using the backup circuit 200 in case of a malfunction of the NO delivery device 1, the same accuracy of inhaled NO concentration is not guaranteed as when the NO delivery system 1 operates in normal operation, i.e. by adjusting the NO flow rate according to the flow rate passing through the flow sensor 100, but this avoids a break in the supply of NO to the patient and, moreover, the buffer volume generated by the portion of the inspiratory branch 31 located downstream of the NO injection module, which is possibly increased by the volume of the humidification chamber when present, makes it possible to smooth out the variations in the concentration of NO inhaled by the patient and to get closer to the desired target value, i.e. the NO dosage.

[0141] The emergency dosing system of the invention is therefore particularly interesting to implement because it increases safety for the patient who does not risk being deprived of their NO treatment in the event of a malfunction of the NO delivery device, and receives a dose of NO very close to, or even equal to, the desired dosage.

[0142] In other words, being able to approach the desired target NO value using the NO 200 backup dosing system integrated into the NO delivery device 1 of the invention significantly improves patient safety compared with a fixed backup NO flow rate usually delivered by the safety system of prior art NO delivery devices.

[0143] Thus, by way of comparison, with a backup system based on a fixed flow rate, such as is classically implemented in prior art NO delivery devices: For an average NO flow rate of 0.05 L / min required to normally maintain an NO concentration of 10 ppmv (use case in neonatology with an HFO-type ventilator), the resulting concentration with the fixed flow rate is 50 ppmv, which corresponds to a fivefold increase in the desired dosage. Conversely, for an average NO flow rate of 1 L / min required to maintain an NO concentration of 80 ppmv (use case in adults, for example, in cases of pulmonary hypertension during cardiac surgery), the resulting concentration drops to 20 ppmv, which corresponds to a 75% reduction in the desired dosage.

[0144] In both cases, significant dosage deviations can lead to unacceptable and dangerous situations for the patient, unlike the NO 200 emergency dosing system integrated into the NO delivery device 1 of the invention, which allows the desired dosage to be respected.

[0145] It follows that the NO 200 emergency dosing system of the invention offers undeniable advantages in enhancing patient safety by: automatically injecting a backup flow of NO without waiting for the user to realize the situation and intervene by switching to pneumatic backup dosing, ensuring that the concentration of NO inhaled by the patient is similar to the concentration desired by the physician, i.e., the desired dosage.

[0146] Of course, the switch to the NO 200 emergency dosing system of the invention is only temporary, that is to say, it only lasts for the time necessary to replace the faulty equipment or component which triggered the audible and / or visual alarm system in order to alert the care staff.

[0147] To prevent the accidental activation of the NO backup dosing system 200, the control unit 130 is further configured to perform appropriate initialization and shutdown sequences. For example, if the user intentionally stops the NO therapy, the control unit 130 can command the actuator 203 to close the pressure regulator 204. Thus, if the system is intentionally shut down and the solenoid valve 202 is opened, the "closed" configuration of the pressure regulator 204 prevents any flow of NO in the backup line 201 until the NO delivery device 1 has shut down.

[0148] The NO 1 delivery device equipped with the NO 200 emergency dosing system of the invention is particularly well suited to supplying gas mixtures comprising 1 to 80 ppmv of NO and at least 20% vol. of oxygen to patients (adults, children, adolescents or newborns), preferably at least 21% vol. of oxygen, suffering from pulmonary hypertension and / or hypoxia, which may cause pulmonary vasoconstrictions or similar conditions, for example caused by pulmonary pathologies or disorders such as PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or caused by cardiac surgery with extracorporeal blood circulation.

Claims

1. NO delivery device (1) for supplying a gas containing NO, in particular an NO / N2 gas mixture, comprising: - an NO injection line (111) for conveying the NO-containing gas, - a valve device (113) arranged on the injection line (111) to control the flow of the NO-containing gas in the injection line (111), said valve device (113) being configured to be normally in a closed position to prevent any gas flow in the injection line (111), - a flow measurement device (112) arranged on the injection line (111) to measure the flow rate of the NO-containing gas flowing in the injection line (111), - a backup circuit (200) comprising a backup line (201) fluidly connected to the injection line (111), upstream (111a) and downstream (111b) of the valve device (113), said backup line (201) comprising a backup solenoid valve (202) configured to be normally in an open position to allow gas to flow through the backup line (201), and a flow control device (210), and - control means (130) configured to cooperate with the emergency solenoid valve (202), the flow control device (210), the valve device (113) and the flow measurement device (112), and wherein, in the event of a malfunction causing a failure of cooperation with the control means (130): - the emergency solenoid valve (202) is configured to switch to the open position to allow gas to flow through the emergency line (201) of the emergency circuit (200), - the valve device (113) is configured to switch to the closed position to stop all gas flow in the injection line (111), and - the flow control device (210) is configured to supply gas at a preset emergency gas flow rate, wherein said emergency gas flow rate: ∘ is determined by the control means (130) from at least one gas flow measurement provided by the flow measurement device (112) during normal operation of the device (1) preceding said malfunction, and ∘ is preset by control of said flow control device (210) by the control means (130) during said normal operation of the device (1), characterized in that: - a multi-way solenoid valve (205) is arranged on the backup line (201), downstream of the flow control device (210), - said multi-way solenoid valve (205) comprising: ∘ an inlet port fluidically connected to the backup line (201) downstream of the flow control device (210), ∘ a first outlet port fluidly connected to a first metering line (206) comprising a first calibrated orifice device (208), and ∘ a second outlet port fluidly connected to a second metering line (207) comprising a second calibrated orifice device (209), - the first metering line (206) and the second metering line (207) connect (201b) to the backup line (201) downstream of said first and second calibrated orifice devices (208, 209), - the first and second calibrated orifice devices (208, 209) have calibrated orifices (D1, D2) with different passage cross-sections or diameters, - and the control means (130) are configured to control the multi-way solenoid valve (205) to direct the gas flow to the first metering line (206) or, alternatively, to the second dosing line (207) depending on the gas flow measurement(s) provided by the flow measurement device (112) during normal operation of the device (1) preceding said malfunction.

2. Device according to claim 1, characterized in that the multi-way solenoid valve (205) comprises 3 ways.

3. Device according to claim 1, characterized in that the first calibrated orifice of the first calibrated orifice device (208) has a first passage diameter (D1) and the calibrated orifice of the second calibrated orifice device (209) has a second passage diameter (D2) such that 1.5.D1 < D2 < 4.D1.

4. Device according to claim 3, characterized in that the first passage diameter (D1) and the second passage diameter (D2) are such that: 1.8.D1 < D2 < 3.D1, preferably D2 is equal to approximately 2.D1.

5. Device according to claim 1, characterized in that the backup solenoid valve (202) is of the on / off type that can only adopt an open state in which it allows the gas flow to pass and a closed state in which it interrupts the passage of the gas flow.

6. Device according to claim 1, characterized in that the flow control device (210) comprising an actuator means (203) cooperating with a pneumatic pressure regulator (204), preferably the actuator means (203) comprises a stepper motor.

7. Device according to claim 6, characterized in that: - the pneumatic regulator (204) is configured to be adjustable to several pressure levels between 0 and 2 bar relative, preferably less than 1.5 bar relative, and - the actuator means (203) cooperates with the pneumatic regulator (204) to set a desired outlet pressure downstream of said pneumatic regulator (204).

8. Device according to claim 7, characterized in that: - the pneumatic regulator (204) comprises an internal spring for setting the desired pressure level, and - the actuator means (203) comprises a stepper motor configured to adopt several different angular positions, each angular position of the stepper motor corresponding to a given tension of the internal spring of the pneumatic regulator (204), so that the desired outlet pressure level downstream of the pneumatic regulator (204) is determined by the tension of the internal spring of the pneumatic regulator (204) corresponding to the angular position adopted by the stepper motor.

9. Device according to claim 1, characterized in that, in normal operation, the control means (130) are configured to control the multi-way solenoid valve (205) to operate a fluidic communication between the inlet port of the multi-way solenoid valve (205) and either the first or second outlet port of the multi-port solenoid valve (205) so as to pass the gas flow through the first or second calibrated orifice device (208, 209).

10. Device according to claim 1, characterized in that the control means (130) comprise at least one microprocessor.

11. Device according to claim 1, characterized in that the valve device (113) comprises a proportional solenoid valve.

12. Device according to claim 1, characterized in that the flow measurement device (112) is configured to perform several successive flow measurements during normal operation of the NO delivery device (1).

13. Device according to claims 1 and 6, 7 or 8, characterized in that the control means (130) are configured to determine the opening of the pneumatic pressure regulator (204) and / or the backup flow rate from a correspondence table stored by storage means, such as a computer memory.

14. Gas supply system (1, 2) for a patient, comprising: - at least one NO source (250) containing an NO / N2gas mixture, preferably an NO / N2gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N2), - an NO delivery device (1) according to one of the preceding claims, supplied with NO / N2 gas mixture by said at least one NO source (250), - an inspiratory branch (31) of a patient circuit (3) supplied with a NO / N2 gas mixture by the NO delivery device (1) , and - a medical ventilator (2) in fluid communication with the inspiratory branch (31) to supply said inspiratory branch (31) with a respiratory gas containing at least 20% oxygen, preferably air or an oxygen / nitrogen mixture.